tbuckley/cabot-search huggingface dataset:
ESICM guidelines on acute respiratory distress syndrome: definition, phenotyping and respiratory support strategies
Authors: Giacomo Grasselli, Carolyn S. Calfee, Luigi Camporota, Daniele Poole, Marcelo B. P. Amato, Massimo Antonelli, Yaseen M. Arabi, Francesca Baroncelli, Jeremy R. Beitler, Giacomo Bellani, Geoff Bellingan, Bronagh Blackwood, Lieuwe D. J. Bos, Laurent Brochard, Daniel Brodie, Karen E. A. Burns, Alain Combes, Sonia D’Arrigo, Daniel De Backer, Alexandre Demoule, Sharon Einav, Eddy Fan, Niall D. Ferguson, Jean-Pierre Frat, Luciano Gattinoni, Claude Guérin, Margaret S. Herridge, Carol Hodgson, Catherine L. Hough, Samir Jaber, Nicole P. Juffermans, Christian Karagiannidis, Jozef Kesecioglu, Arthur Kwizera, John G. Laffey, Jordi Mancebo, Michael A. Matthay, Daniel F. McAuley, Alain Mercat, Nuala J. Meyer, Marc Moss, Laveena Munshi, Sheila N. Myatra, Michelle Ng Gong, Laurent Papazian, Bhakti K. Patel, Mariangela Pellegrini, Anders Perner, Antonio Pesenti, Lise Piquilloud, Haibo Qiu, Marco V. Ranieri, Elisabeth Riviello, Arthur S. Slutsky, Renee D. Stapleton, Charlotte Summers, Taylor B. Thompson, Carmen S. Valente Barbas, Jesús Villar, Lorraine B. Ware, Björn Weiss, Fernando G. Zampieri, Elie Azoulay, Maurizio Cecconi
Journal: Intensive Care Medicine (2023)

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to coronavirus disease 2019 (COVID-19). These guidelines were formulated by an international panel of clinical experts, one methodologist and patients’ representatives on behalf of the ESICM. The review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess the certainty of evidence and grade recommendations and the quality of reporting of each study based on the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) network guidelines. The CPG addressed 21 questions and formulates 21 recommendations on the following domains: (1) definition; (2) phenotyping, and respiratory support strategies including (3) high-flow nasal cannula oxygen (HFNO); (4) non-invasive ventilation (NIV); (5) tidal volume setting; (6) positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM); (7) prone positioning; (8) neuromuscular blockade, and (9) extracorporeal life support (ECLS). In addition, the CPG includes expert opinion on clinical practice and identifies the areas of future research.
Phylogenetic Comparative Approach Reveals Evolutionary Conservatism, Ancestral Composition, and Integration of Vertebrate Gut Microbiota
Authors: Benoît Perez-Lamarque, Guilhem Sommeria-Klein, Loréna Duret, Hélène Morlon
Journal: Molecular Biology and Evolution (2023)

How host-associated microbial communities evolve as their hosts diversify remains equivocal: how conserved is their composition? What was the composition of ancestral microbiota? Do microbial taxa covary in abundance over millions of years? Multivariate phylogenetic models of trait evolution are key to answering similar questions for complex host phenotypes, yet they are not directly applicable to relative abundances, which usually characterize microbiota. Here, we extend these models in this context, thereby providing a powerful approach for estimating phylosymbiosis (the extent to which closely related host species harbor similar microbiota), ancestral microbiota composition, and integration (evolutionary covariations in bacterial abundances). We apply our model to the gut microbiota of mammals and birds. We find significant phylosymbiosis that is not entirely explained by diet and geographic location, indicating that other evolutionary-conserved traits shape microbiota composition. We identify main shifts in microbiota composition during the evolution of the two groups and infer an ancestral mammalian microbiota consistent with an insectivorous diet. We also find remarkably consistent evolutionary covariations among bacterial orders in mammals and birds. Surprisingly, despite the substantial variability of present-day gut microbiota, some aspects of their composition are conserved over millions of years of host evolutionary history.
Partial Pressure of Arterial Oxygen in Healthy Adults at High Altitudes
Authors: Aglaia Forrer, Thomas Gaisl, Ahmet Sevik, Michelle Meyer, Luzi Senteler, Mona Lichtblau, Konrad Ernst Bloch, Silvia Ulrich, Michael Furian
Journal: JAMA Network Open (2023)

With increasing altitude, the partial pressure of inspired oxygen decreases and, consequently, the Pao2 decreases. Even though this phenomenon is well known, the extent of the reduction as a function of altitude remains unknown.
Cardiovascular Safety of Testosterone-Replacement Therapy
Authors: A. Michael Lincoff, Shalender Bhasin, Panagiotis Flevaris, Lisa M. Mitchell, Shehzad Basaria, William E. Boden, Glenn R. Cunningham, Christopher B. Granger, Mohit Khera, Ian M. Thompson, Qiuqing Wang, Kathy Wolski, Deborah Davey, Vidyasagar Kalahasti, Nader Khan, Michael G. Miller, Michael C. Snabes, Anna Chan, Elena Dubcenco, Xue Li, Tingting Yi, Bidan Huang, Karol M. Pencina, Thomas G. Travison, Steven E. Nissen
Journal: New England Journal of Medicine (2023)

The cardiovascular safety of testosterone-replacement therapy in middle-aged and older men with hypogonadism has not been determined.In a multicenter, randomized, double-blind, placebo-controlled, noninferiority trial, we enrolled 5246 men 45 to 80 years of age who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels of less than 300 ng per deciliter. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 350 and 750 ng per deciliter) or placebo gel. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, assessed in a time-to-event analysis. A secondary cardiovascular end point was the first occurrence of any component of the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization, assessed in a time-to-event analysis. Noninferiority required an upper limit of less than 1.5 for the 95% confidence interval of the hazard ratio among patients receiving at least one dose of testosterone or placebo.The mean (±SD) duration of treatment was 21.7±14.1 months, and the mean follow-up was 33.0±12.1 months. A primary cardiovascular end-point event occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; 95% confidence interval, 0.78 to 1.17; P<0.001 for noninferiority). Similar findings were observed in sensitivity analyses in which data on events were censored at various times after discontinuation of testosterone or placebo. The incidence of secondary end-point events or of each of the events of the composite primary cardiovascular end point appeared to be similar in the two groups. A higher incidence of atrial fibrillation, of acute kidney injury, and of pulmonary embolism was observed in the testosterone group.In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events. (Funded by AbbVie and others; TRAVERSE ClinicalTrials.gov number, NCT03518034.).
ReporTree: a surveillance-oriented tool to strengthen the linkage between pathogen genetic clusters and epidemiological data
Authors: Verónica Mixão, Miguel Pinto, Daniel Sobral, Adriano Di Pasquale, João Paulo Gomes, Vítor Borges
Journal: Genome Medicine (2023)

Genomics-informed pathogen surveillance strengthens public health decision-making, playing an important role in infectious diseases' prevention and control. A pivotal outcome of genomics surveillance is the identification of pathogen genetic clusters and their characterization in terms of geotemporal spread or linkage to clinical and demographic data. This task often consists of the visual exploration of (large) phylogenetic trees and associated metadata, being time-consuming and difficult to reproduce.
Activation of the Aryl Hydrocarbon Receptor in Muscle Exacerbates Ischemic Pathology in Chronic Kidney Disease
Authors: Nicholas Balestrieri, Victoria Palzkill, Caroline Pass, Jianna Tan, Zachary R. Salyers, Chatick Moparthy, Ania Murillo, Kyoungrae Kim, Trace Thome, Qingping Yang, Kerri A. O’Malley, Scott A. Berceli, Feng Yue, Salvatore T. Scali, Leonardo F. Ferreira, Terence E. Ryan
Journal: Circulation Research (2023)

Chronic kidney disease (CKD) accelerates the development of atherosclerosis, decreases muscle function, and increases the risk of amputation or death in patients with peripheral artery disease (PAD). However, the mechanisms underlying this pathobiology are ill-defined. Recent work has indicated that tryptophan-derived uremic solutes, which are ligands for AHR (aryl hydrocarbon receptor), are associated with limb amputation in PAD. Herein, we examined the role of AHR activation in the myopathy of PAD and CKD.
<i>N</i> 6-methyladenosine Modification of FZR1 mRNA Promotes Gemcitabine Resistance in Pancreatic Cancer
Authors: Jiachun Su, Rui Li, Ziming Chen, Shaoqiu Liu, Hongzhe Zhao, Shuang Deng, Lingxing Zeng, Zilan Xu, Sihan Zhao, Yifan Zhou, Mei Li, Xiaowei He, Ji Liu, Chunling Xue, Ruihong Bai, Lisha Zhuang, Quanbo Zhou, Shaoping Zhang, Rufu Chen, Xudong Huang, Dongxin Lin, Jian Zheng, Jialiang Zhang
Journal: Cancer Research (2023)

Abstract The therapeutic options for treating pancreatic ductal adenocarcinoma (PDAC) are limited, and resistance to gemcitabine, a cornerstone of PDAC chemotherapy regimens, remains a major challenge. N6-methyladenosine (m6A) is a prevalent modification in mRNA that has been linked to diverse biological processes in human diseases. Herein, by characterizing the global m6A profile in a panel of gemcitabine-sensitive and gemcitabine-insensitive PDAC cells, we identified a key role for elevated m6A modification of the master G0–G1 regulator FZR1 in regulating gemcitabine sensitivity. Targeting FZR1 m6A modification augmented the response to gemcitabine treatment in gemcitabine-resistant PDAC cells both in vitro and in vivo. Mechanistically, GEMIN5 was identified as a novel m6A mediator that specifically bound to m6A-modified FZR1 and recruited the eIF3 translation initiation complex to accelerate FZR1 translation. FZR1 upregulation maintained the G0–G1 quiescent state and suppressed gemcitabine sensitivity in PDAC cells. Clinical analysis further demonstrated that both high levels of FZR1 m6A modification and FZR1 protein corresponded to poor response to gemcitabine. These findings reveal the critical function of m6A modification in regulating gemcitabine sensitivity in PDAC and identify the FZR1–GEMIN5 axis as a potential target to enhance gemcitabine response. Significance: Increased FZR1 translation induced by m6A modification engenders a gemcitabine-resistant phenotype by inducing a quiescent state and confers a targetable vulnerability to improve treatment response in PDAC.
Relationship between COVID-19 and ICU-acquired colonization and infection related to multidrug-resistant bacteria: a prospective multicenter before-after study
Authors: Louis Kreitmann, Sonia Jermoumi, Margot Vasseur, Myriam Chabani, Emilie Nourry, Jean-Christophe Richard, Florent Wallet, Pierre Garçon, Safaâ Kachmar, Yoann Zerbib, Nicolas Van Grunderbeeck, Christophe Vinsonneau, Alain Duhamel, Julien Labreuche, Saad Nseir
Journal: Intensive Care Medicine (2023)
Molecular mechanisms of tumor resistance to radiotherapy
Authors: Yu Wu, Yingqiu Song, Runze Wang, Tianlu Wang
Journal: Molecular Cancer (2023)

Abstract Background Cancer is the most prevalent cause of death globally, and radiotherapy is considered the standard of care for most solid tumors, including lung, breast, esophageal, and colorectal cancers and glioblastoma. Resistance to radiation can lead to local treatment failure and even cancer recurrence. Main body In this review, we have extensively discussed several crucial aspects that cause resistance of cancer to radiation therapy, including radiation-induced DNA damage repair, cell cycle arrest, apoptosis escape, abundance of cancer stem cells, modification of cancer cells and their microenvironment, presence of exosomal and non-coding RNA, metabolic reprogramming, and ferroptosis. We aim to focus on the molecular mechanisms of cancer radiotherapy resistance in relation to these aspects and to discuss possible targets to improve treatment outcomes. Conclusions Studying the molecular mechanisms responsible for radiotherapy resistance and its interactions with the tumor environment will help improve cancer responses to radiotherapy. Our review provides a foundation to identify and overcome the obstacles to effective radiotherapy.
Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis
Authors: Dustin G. Shaw, Raúl Aguirre-Gamboa, Marcos C. Vieira, Saideep Gona, Nicholas DiNardi, Anni Wang, Anne Dumaine, Jody Gelderloos-Arends, Zachary M. Earley, Katherine R. Meckel, Cezary Ciszewski, Anabella Castillo, Kelly Monroe, Joana Torres, Shailja C. Shah, Jean-Frédéric Colombel, Steven Itzkowitz, Rodney Newberry, Russell D. Cohen, David T. Rubin, Christopher Quince, Sarah Cobey, Iris H. Jonkers, Christopher R. Weber, Joel Pekow, Patrick C. Wilson, Luis B. Barreiro, Bana Jabri
Journal: Nature Medicine (2023)

Abstract Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia in patients with PSC. This inflammatory signature is characterized by antigen-driven interleukin-17A (IL-17A) + forkhead box P3 (FOXP3) + CD4 T cells that express a pathogenic IL-17 signature, as well as an expansion of IgG-secreting plasma cells. These results suggest that the mechanisms that drive the emergence of dysplasia in PSC and IBD are distinct and provide molecular insights that could guide prevention of colorectal cancer in individuals with PSC.
Nanoparticle-Based Combination Therapy Enhances Fulvestrant Efficacy and Overcomes Tumor Resistance in ER-Positive Breast Cancer
Authors: Bozhao Li, Feilong Qi, Fei Zhu, Zefang Lu, Meiqi Wang, Tianjiao Chu, Suying Wu, Jingyan Wei, Zhenchuan Song, Saraswati Sukumar, Cheng Zhang, Jiangfei Xu, Suping Li, Guangjun Nie
Journal: Cancer Research (2023)

Nanoparticles (NP) spanning diverse materials and properties have the potential to encapsulate and to protect a wide range of therapeutic cargos to increase bioavailability, to prevent undesired degradation, and to mitigate toxicity. Fulvestrant, a selective estrogen receptor degrader, is commonly used for treating patients with estrogen receptor (ER)-positive breast cancer, but its broad and continual application is limited by poor solubility, invasive muscle administration, and drug resistance. Here, we developed an active targeting motif-modified, intravenously injectable, hydrophilic NP that encapsulates fulvestrant to facilitate its delivery via the bloodstream to tumors, improving bioavailability and systemic tolerability. In addition, the NP was coloaded with abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), to prevent the development of drug resistance associated with long-term fulvestrant treatment. Targeting peptide modifications on the NP surface assisted in the site-specific release of the drugs to ensure specific toxicity in the tumor tissues and to spare normal tissue. The NP formulation (PPFA-cRGD) exhibited efficient tumor cell killing in both in vitro organoid models and in vivo orthotopic ER-positive breast cancer models without apparent adverse effects, as verified in mouse and Bama miniature pig models. This NP-based therapeutic provides an opportunity for continual and extensive clinical application of fulvestrant, thus indicating its promise as a treatment option for patients with ER-positive breast cancer.A smart nanomedicine encapsulating fulvestrant to improve its half-life, bioavailability, and tumor-targeting and coloaded with CDK4/6 inhibitor abemaciclib to block resistance is a safe and effective therapy for ER-positive breast cancer.
Video Laryngoscopy for Intubation — Time for a New Paradigm?
Authors: Yonathan Freund, Ben Bloom
Journal: New England Journal of Medicine (2023)

Endotracheal intubation — a potentially lifesaving procedure that is used for the care of many critically ill patients — demands precision, speed, and skill. It involves the placement of a tube into the trachea to protect the airways while ensuring adequate oxygenation and ventilation for patients who are in respiratory distress or are unable to breathe effectively on their own (or both). Historically, direct laryngoscopy has been the favored technique, in which practitioners use a laryngoscope blade to visualize the larynx directly through the mouth in order to correctly position the endotracheal tube for insertion. Video laryngoscopy has emerged as . . .
Genomic Surveillance for SARS-CoV-2 Variants: Circulation of Omicron Lineages — United States, January 2022–May 2023
Authors: Kevin C. Ma, Philip Shirk, Anastasia S. Lambrou, Norman Hassell, Xiao-yu Zheng, Amanda B. Payne, Akilah R. Ali, Dhwani Batra, Jason Caravas, Reina Chau, Peter W. Cook, Dakota Howard, Nicholas A. Kovacs, Kristine A. Lacek, Justin S. Lee, Duncan R. MacCannell, Lakshmi Malapati, Sandra Mathew, Neha Mittal, Roopa R. Nagilla, Rishika Parikh, Prabasaj Paul, Benjamin L. Rambo-Martin, Samuel S. Shepard, Mili Sheth, David E. Wentworth, Amber Winn, Aron J. Hall, Benjamin J. Silk, Natalie Thornburg, Rebecca Kondor, Heather M. Scobie, Clinton R. Paden
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

CDC has used national genomic surveillance since December 2020 to monitor SARS-CoV-2 variants that have emerged throughout the COVID-19 pandemic, including the Omicron variant. This report summarizes U.S. trends in variant proportions from national genomic surveillance during January 2022-May 2023. During this period, the Omicron variant remained predominant, with various descendant lineages reaching national predominance (>50% prevalence). During the first half of 2022, BA.1.1 reached predominance by the week ending January 8, 2022, followed by BA.2 (March 26), BA.2.12.1 (May 14), and BA.5 (July 2); the predominance of each variant coincided with surges in COVID-19 cases. The latter half of 2022 was characterized by the circulation of sublineages of BA.2, BA.4, and BA.5 (e.g., BQ.1 and BQ.1.1), some of which independently acquired similar spike protein substitutions associated with immune evasion. By the end of January 2023, XBB.1.5 became predominant. As of May 13, 2023, the most common circulating lineages were XBB.1.5 (61.5%), XBB.1.9.1 (10.0%), and XBB.1.16 (9.4%); XBB.1.16 and XBB.1.16.1 (2.4%), containing the K478R substitution, and XBB.2.3 (3.2%), containing the P521S substitution, had the fastest doubling times at that point. Analytic methods for estimating variant proportions have been updated as the availability of sequencing specimens has declined. The continued evolution of Omicron lineages highlights the importance of genomic surveillance to monitor emerging variants and help guide vaccine development and use of therapeutics.
Uterus transplantation: from research, through human trials and into the future
Authors: Mats Brännström, Catherine Racowsky, Marie Carbonnel, Joseph Wu, Antonio Gargiulo, Eli Y Adashi, Jean Marc Ayoubi
Journal: Human Reproduction Update (2023)

Abstract Women suffering from absolute uterine factor infertility (AUFI) had no hope of childbearing until clinical feasibility of uterus transplantation (UTx) was documented in 2014 with the birth of a healthy baby. This landmark accomplishment followed extensive foundational work with a wide range of animal species including higher primates. In the present review, we provide a summary of the animal research and describe the results of cases and clinical trials on UTx. Surgical advances for graft removal from live donors and transplantation to recipients are improving, with a recent trend away from laparotomy to robotic approaches, although challenges persist regarding optimum immunosuppressive therapies and tests for graft rejection. Because UTx does not involve transplantation of the Fallopian tubes, IVF is required as part of the UTx process. We provide a unique focus on the intersection between these two processes, with consideration of when oocyte retrieval should be performed, whether, and for whom, preimplantation genetic testing for aneuploidy should be used, whether oocytes or embryos should be frozen and when the first embryo transfer should be performed post-UTx. We also address the utility of an international society UTx (ISUTx) registry for assessing overall UTx success rates, complications, and live births. The long-term health outcomes of all parties involved—the uterus donor (if live donor), the recipient, her partner and any children born from the transplanted graft—are also reviewed. Unlike traditional solid organ transplantation procedures, UTx is not lifesaving, but is life-giving, although as with traditional types of transplantation, costs, and ethical considerations are inevitable. We discuss the likelihood that costs will decrease as efficiency and efficacy improve, and that ethical complexities for and against acceptability of the procedure sharpen the distinctions between genetic, gestational, and social parenthood. As more programs wish to offer the procedure, we suggest a scheme for setting up a UTx program as well as future directions of this rapidly evolving field. In our 2010 review, we described the future of clinical UTx based on development of the procedure in animal models. This Grand Theme Review offers a closing loop to this previous review of more than a decade ago. The clinical feasibility of UTx has now been proved. Advancements include widening the criteria for acceptance of donors and recipients, improving surgery, shortening time to pregnancy, and improving post-UTx management. Together, these improvements catalyze the transition of UTx from experimental into mainstream clinical practice. The procedure will then represent a realistic and accessible alternative to gestational surrogacy for the treatment of AUFI and should become part of the armamentarium of reproductive specialists worldwide.
Global Incidence and Prevalence of Eosinophilic Esophagitis, 1976–2022: A Systematic Review and Meta-analysis
Authors: Jong Woo Hahn, Kwanjoo Lee, Jae Il Shin, Seong Ho Cho, Stephen Turner, Jung U Shin, Abdullah Özgür Yeniova, Ai Koyanagi, Louis Jacob, Lee Smith, Guillaume Fond, Laurent Boyer, Seung Won Lee, Rosie Kwon, Soeun Kim, Youn Ho Shin, Sang Youl Rhee, Jin Soo Moon, Jae Sung Ko, Dong Keon Yon, Nikolaos G. Papadopoulos
Journal: Clinical Gastroenterology and Hepatology (2023)